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Which One Among Aspartyl Protease, Metallopeptidase, and Artificial Metallopeptidase is the Most Efficient Catalyst in Peptide Hydrolysis?

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journal contribution
posted on 26.08.2010, 00:00 by Ram Prasad Bora, Arghya Barman, Xiaoxia Zhu, Mehmet Ozbil, Rajeev Prabhakar
In this comparative DFT study, the hydrolysis of a peptide bond (Phe1-Phe2) by the following three types of catalysts has been studied: (1) β-secretase (BACE2), (2) matrix metalloproteinase (MMP) and insulin degrading enzyme (IDE), and (3) [Pd(H2O)4]2+ (IMPC) and [Pd2(μ-OH)([18]aneN6)]3+ (IDPC). The computed energetics predict that among these catalysts, the Zn2+ metal center containing MMP is the most efficient in catalyzing this reaction. The two active site aspartate residues containing BACE2 catalyze this reaction with 5.0 kcal/mol higher barrier than MMP. The substitution of a His ligand with Glu in the metal center of MMP generates the active site of IDE that catalyzes the reaction with a 6.9 kcal/mol higher barrier than MMP. Both artificial peptidases IMPC and IDPC catalyze this reaction with significantly high barriers of 35.4 and 31.0 kcal/mol, respectively. The computed energetics of all the catalysts are in line with the available experimental and theoretical data.